This invention relates to the field of pharmaceutical chemistry, and provides an advantageous process for preparing a group of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-aminoethoxy)benzoyl]benzo[.beta.]thi ophenes. More specifically, the invention relates to methods for preparing 2-aminobenzo[.beta.]thiophenes, novel 2-amino-3-aroyl-benzo[.beta.]thiophenes, and the subsequent conversion of those thiophenes to the corresponding 2-(4-hydroxyphenyl) derivatives.
Kobayashi et al., Chem. Lett., 537-540 (1991) teach the preparation of cyanohydrin trimethyl silyl ethers from aldehydes and trimethylsilyl cyamide (TMSCN). Creary and Mohammadi, J. Org. Chem., 51: 7-15 (1986) describe the conversion of various cyanohydrins to the corresponding .alpha.-hydroxythioacetamides.
Ablenas et al., Can. J. Chem. 65: 1800-1803 (1987) teach the preparation of various 2-aryl-2-hydroxy thioacetamides and their subsequent cyclization to benzo[.beta.]thiophenes with methane sulfonic acid (MeSO.sub.3 H).
Chippendale et al., J. C. S. Perkin I, 1168-1172 (1976) disclose the preparation of certain 2- and 3-(secondary amino)benzo[.beta.]thiophenes.
Most of the compounds prepared by the process of this invention are taught in U.S. Pat. No. 4,133,814.